Enantioselective Dynamic Process Reduction of α- and β-Tetralone and Stereoinversion of Resulting Alcohols in a Selected Strain Culture

Abstract

α-Tetralone and β-tetralone were subjected to biotransformation by 14 fungal strains. Enantiomeric purity of the products depended on the reaction time. 3-Day transformation of α-tetralone in Absidia cylindrospora culture gave S-(+)-1,2,3,4-tetrahydro-1-naftol of 92 % ee, whereas longer biotransformation time resulted in decrease of ee value. 3-Day transformation of β-tetralone by the same strain gave predominantly S-(−)-1,2,3,4-tetrahydro-2-naftol, whereas after 9 days of the reaction, the R-enantiomer with 85 % ee was isolated. Transformation of β-tetralone by Chaetomium sp. KCh 6651 gave pure (S)-(−)-1,2,3,4-tetrahydro-2-naftol in high yield at the concentration of 1 g/l. In this process, a non-selective carbonyl reduction was observed, followed by a selective oxidation of the R-alcohol.

Stereochemistry in Asymmetric Reduction of Bulky–Bulky Ketones by Alcohol Dehydrogenases

“…In contrast to diaryl methanone, tetralones that carry different substituents belong to another series of bulky ketones (Figure ). The skeleton structure of these substrates is tetralin, a derivative of the fused ring compound naphthalene, the corresponding chiral alcohols of which are extremely valuable for the synthesis of many serotonin and dopamine agonists. − Several microorganisms, including Absidia cylindrospora , Saccharomyces brasiliensis , and Chaetomium sp. can catalyze the reduction of 1-tetralones ( 65 ) and 2-tetralones ( 54 ) into corresponding ( S )-alcohols .…”

“…The skeleton structure of these substrates is tetralin, a derivative of the fused ring compound naphthalene, the corresponding chiral alcohols of which are extremely valuable for the synthesis of many serotonin and dopamine agonists. − Several microorganisms, including Absidia cylindrospora , Saccharomyces brasiliensis , and Chaetomium sp. can catalyze the reduction of 1-tetralones ( 65 ) and 2-tetralones ( 54 ) into corresponding ( S )-alcohols . In 2002, Kroutil’s research group found 2-tetralone ( 54 ) can be reduced to corresponding ( S )-alcohol with 83% ee by lyophilized cells of Rhodococcus ruber DSM 44541 .…”

Biocatalytic asymmetric synthesis of (R)‐1‐tetralol using Lactobacillus paracasei BD101

“…26 It was reported that (S)-2 was manufactured with 100% ee using the biocatalyst of whole-cell Aquilegia coerulea KCh 93, but the conversion is very low (19%). 27 They also reported that with increasing reaction time, conversion increased, but ee decreased significantly. For example, after 9 days of reaction, (S)-2 was obtained in 76% yield, but in low ee (50%).…”

“…In the study performed with Pisum sativa whole‐cell biocatalyst, it was reported that ( S )‐2 was synthesized with 40% yield and 87% ee 26 . It was reported that ( S )‐2 was manufactured with 100% ee using the biocatalyst of whole‐cell Aquilegia coerulea KCh 93, but the conversion is very low (19%) 27 . They also reported that with increasing reaction time, conversion increased, but ee decreased significantly.…”

Asymmetric Reduction of Substituted 2‐Tetralones by Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase

“…For example, methoxy‐substituted 2‐tetralols have various degrees of biological importance through their ability to inhibit tubulin assembly . Enantiomerically pure ( S )‐2‐tetralol and its hydroxy and alkoxy analogs are used in the synthesis of various drugs that target many central nervous system disorders including 2‐aminotetralins, which exhibit dopamine‐receptor stimulating activity . ( S )‐6‐Chloro‐2‐tetralol is a main building block for the drug MK‐0499, which can be used as a potassium channel blocker for the treatment of ventricular arrhythmias or as a polarization mediator of cardiac tissues …”